Epoprostenol is a chemical class of prostaglandins within the eicosanoids family of lipid molecules. It is a potent vasodilator and responsible for platelet activation. It is used to treat patients with pulmonary arterial hypertension (PAH) and to improve exercise ability and reduce clinical worsening. In the United States, it is manufactured and marketed by Glaxo Smith Kline under the trade name Flolan and by Actelion Pharmaceuticals under the name Veletri. It is sold as a powder, diluted in a solution, and then injected.
How Epoprostenol Works
Prostaglandin is biosynthesized in the human vascular tissues easily and has a paracrine mode of signaling on localized G protein-coupled receptors on endothelial cells and platelets. The platelets get activated on binding to PGI2 and activates adenylyl cyclase to produce cAMP. It then prevents undue platelet activation and counteracts production of excess calcium. Meanwhile, the binding of PGI2 to G protein-coupled receptors on endothelial cells increases cAMP levels in the cytosol, the latter activating protein kinase A (PKA). PKA is then involved in a series of dephosphorylation reactions which eventually causes the smooth muscles to relax toward vasodilation.
The Flolan and Veletri Formulations of Epoprostenol for PAH
Flolan was approved by the FDA in September 1995, followed by Veletri in June 2008. Both are injected into the patient’s bloodstream, either via syringe or ambulatory infusion pumps. Dosage using infusion pumps is ideally started with intravenous infusions of 2 ng/kg/min with subsequent increments in the doses by 1- to 2-ng/kg/min with at least 15 minutes intervals between consecutive doses (until dose-related side-effects occur or if advised otherwise by the physician). For an injection 0.5 mg or 1.5 mg of epoprostenol, freeze-dried powder in a single-dose vial is reconstituted with the supplied diluent.
Adverse reactions reported during clinical trials for both drugs included flushing, headache, nausea, vomiting, low blood pressure, jaw pain, anxiety and nervousness, chest pain, dizziness, slow heartbeat, abdominal pain, pain in the muscles, ligaments and bones; shortness of breath, back pain, sweating, upset stomach, numbness, increased sensitivity, and fast heartbeat. Some severe side-effects include bleeding, thrombocytopenia, chest pain, fatigue, and pallor. Patients on diuretics, anticoagulants and anti-platelet medicines are advised to consult a specialist before taking the drug. Pregnant women or those planning to conceive are strictly advised against taking the drug.
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